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Yiheng Tu

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14 papers
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14

NeurIPS Conference 2022 Conference Paper

A Simple Approach to Automated Spectral Clustering

  • Jicong Fan
  • Yiheng Tu
  • Zhao Zhang
  • Mingbo Zhao
  • Haijun Zhang

The performance of spectral clustering heavily relies on the quality of affinity matrix. A variety of affinity-matrix-construction (AMC) methods have been proposed but they have hyperparameters to determine beforehand, which requires strong experience and leads to difficulty in real applications, especially when the inter-cluster similarity is high and/or the dataset is large. In addition, we often need to choose different AMC methods for different datasets, which still depends on experience. To solve these two challenging problems, in this paper, we present a simple yet effective method for automated spectral clustering. First, we propose to find the most reliable affinity matrix via grid search or Bayesian optimization among a set of candidates given by different AMC methods with different hyperparameters, where the reliability is quantified by the \textit{relative-eigen-gap} of graph Laplacian introduced in this paper. Second, we propose a fast and accurate AMC method based on least squares representation and thresholding and prove its effectiveness theoretically. Finally, we provide a large-scale extension for the automated spectral clustering method, of which the time complexity is linear with the number of data points. Extensive experiments of natural image clustering show that our method is more versatile, accurate, and efficient than baseline methods.

YNIMG Journal 2021 Journal Article

How expectations of pain elicited by consciously and unconsciously perceived cues unfold over time

  • Yiheng Tu
  • Dimitrios Pantazis
  • Georgia Wilson
  • Sheraz Khan
  • Seppo Ahlfors
  • Jian Kong

Expectation can shape the perception of pain within a fraction of time, but little is known about how perceived expectation unfolds over time and modulates pain perception. Here, we combine magnetoencephalography (MEG) and machine learning approaches to track the neural dynamics of expectations of pain in healthy participants with both sexes. We found that the expectation of pain, as conditioned by facial cues, can be decoded from MEG as early as 150 ms and up to 1100 ms after cue onset, but decoding expectation elicited by unconsciously perceived cues requires more time and decays faster compared to consciously perceived ones. Also, results from temporal generalization suggest that neural dynamics of decoding cue-based expectation were predominately sustained during cue presentation but transient after cue presentation. Finally, although decoding expectation elicited by consciously perceived cues were based on a series of time-restricted brain regions during cue presentation, decoding relied on the medial prefrontal cortex and anterior cingulate cortex after cue presentation for both consciously and unconsciously perceived cues. These findings reveal the conscious and unconscious processing of expectation during pain anticipation and may shed light on enhancing clinical care by demonstrating the impact of expectation cues.

YNIMG Journal 2021 Journal Article

Perturbing fMRI brain dynamics using transcranial direct current stimulation

  • Yiheng Tu
  • Jin Cao
  • Seyhmus Guler
  • Thalia Chai-Zhang
  • Joan A. Camprodon
  • Mark Vangel
  • Randy L. Gollub
  • Darin D. Dougherty

The dynamic nature of resting-state functional magnetic resonance imaging (fMRI) brain activity and connectivity has drawn great interest in the past decade. Specific temporal properties of fMRI brain dynamics, including metrics such as occurrence rate and transitions, have been associated with cognition and behaviors, indicating the existence of mechanism distruption in neuropsychiatric disorders. The development of new methods to manipulate fMRI brain dynamics will advance our understanding of these pathophysiological mechanisms from native observation to experimental mechanistic manipulation. In the present study, we applied repeated transcranial direct current stimulation (tDCS) to the right dorsolateral prefrontal cortex (rDLPFC) and the left orbitofrontal cortex (lOFC), during multiple simultaneous tDCS-fMRI sessions from 81 healthy participants to assess the modulatory effects of stimulating target brain regions on fMRI brain dynamics. Using the rDLPFC and the lOFC as seeds, respectively, we first identified two reoccurring co-activation patterns (CAPs) and calculated their temporal properties (e.g., occurrence rate and transitions) before administering tDCS. The spatial maps of CAPs were associated with different cognitive and disease domains using meta-analytical decoding analysis. We then investigated how active tDCS compared to sham tDCS in the modulation of the occurrence rates of these different CAPs and perturbations of transitions between CAPs. We found that by enhancing neuronal excitability of the rDLPFC and the lOFC, the occurrence rate of one CAP was significantly decreased while that of another CAP was significantly increased during the first 6 min of stimulation. Furthermore, these tDCS-associated changes persisted over subsequent testing sessions (both during and before/after tDCS) across three consecutive days. Active tDCS could perturb transitions between CAPs and a non-CAP state (when the rDLPFC and the lOFC were not activated), but not the transitions within CAPs. These results demonstrate the feasibility of modulating fMRI brain dynamics, and open new possibilities for discovering stimulation targets and dynamic connectivity patterns that can ensure the propagation of tDCS-induced neuronal excitability, which may facilitate the development of new treatments for disorders with altered dynamics.

YNIMG Journal 2021 Journal Article

The role of negative emotions in sex differences in pain sensitivity

  • Huijuan Zhang
  • Yanzhi Bi
  • Xin Hou
  • Xuejing Lu
  • Yiheng Tu
  • Li Hu

Pain perception varies widely among individuals due to the varying degrees of biological, psychological, and social factors. Notably, sex differences in pain sensitivity have been consistently observed in various experimental and clinical investigations. However, the neuropsychological mechanism underlying sex differences in pain sensitivity remains unclear. To address this issue, we quantified pain sensitivity (i.e., pain threshold and tolerance) using the cold pressure test and negative emotions (i.e., pain-related fear, pain-related anxiety, trait anxiety, and depression) using well-established questionnaires and collected magnetic resonance imaging (MRI) data (i.e., high-resolution T1 structural images and resting-state functional images) from 450 healthy subjects. We observed that, as compared to males, females exhibited lower pain threshold and tolerance. Notably, sex differences in pain sensitivity were mediated by pain-related fear and anxiety. Specifically, pain-related fear and anxiety were the complementary mediators of the relationship between sex and pain threshold, and they were the indirect-only mediators of the relationship between sex and pain tolerance. Besides, structural MRI data revealed that the amygdala subnuclei (i.e., the lateral and basal nuclei in the left hemisphere) volumes were the complementary mediators of the relationship between sex and pain-related fear, which further influenced pain sensitivity. Altogether, our results provided a comprehensive picture of how negative emotions (especially pain-related negative emotions) and related brain structures (especially the amygdala) contribute to sex differences in pain sensitivity. These results deepen our understanding of the neuropsychological underpinnings of sex differences in pain sensitivity, which is important to tailor a personalized method for treating pain according to sex and the level of pain-related negative emotions for patients with painful conditions.

YNIMG Journal 2020 Journal Article

Characterizing the analgesic effects of real and imagined acupuncture using functional and structure MRI

  • Jin Cao
  • Yiheng Tu
  • Georgia Wilson
  • Scott P. Orr
  • Jian Kong

Acupuncture and imagery interventions for pain management have a long history. The present study comparatively investigated whether acupuncture and video-guided acupuncture imagery treatment (VGAIT, watching a video of acupuncture on the participant's own body while imagining it being applied) could modulate brain regional connectivity to produce analgesic effects. The study also examined whether pre-intervention brain functional and structural features could be used to predict the magnitude of analgesic effects. Twenty-four healthy participants were recruited and received four different interventions (real acupuncture, sham acupuncture, VGAIT, and VGAIT control) in random order using a cross-over design. Pain thresholds and magnetic resonance imaging (MRI) data were collected before and after each intervention. We first compared the modulatory effects of real acupuncture and VGAIT on intra- and inter-regional intrinsic brain connectivity and found that real acupuncture decreased regional homogeneity (ReHo) and functional connectivity (FC) in sensorimotor areas, whereas VGAIT increased ReHo in basal ganglia (BG) (i.e., putamen) and FC between the BG subcortical network and default mode network. The altered ReHo and FC were associated with changes in pain threshold after real acupuncture and VGAIT, respectively. A multimodality fusion approach with pre-intervention ReHo and gray matter volume (GMV) as features was used to explore the brain profiles underlying individual variability of pain threshold changes by real acupuncture and VGAIT. Variability in acupuncture responses was associated with ReHo and GMV in BG, whereas VGAIT responses were associated with ReHo and GMV in the anterior insula. These results suggest that, through different pathways, both real acupuncture and VGAIT can modulate brain systems to produce analgesic effects.

YNICL Journal 2020 Journal Article

Corrigendum to “Multivariate resting-state functional connectivity predicts responses to real and sham acupuncture treatment in chronic low back pain” [Neuroimage Clinical 23 (2019) 101885]

  • Yiheng Tu
  • Ana Ortiz
  • Randy L. Gollub
  • Jin Cao
  • Jessica Gerber
  • Courtney Lang
  • Joel Park
  • Georgia Wilson

The authors regret to find several errors that do not influence the main findings or conclusions.Specifically, we have found that the values of pre-and post-treatment clinical sub-scores for 'physical function' and 'sleep' in Fig. 4 contain errors.The corrected Fig. 4 is shown below: As a result, the Results section 3.3 (Page 6, right column): "Real and sham acupuncture significantly reduced PROMIS sub-scores in

YNIMG Journal 2019 Journal Article

A neural mechanism of direct and observational conditioning for placebo and nocebo responses

  • Yiheng Tu
  • Joel Park
  • Seppo P. Ahlfors
  • Sheraz Khan
  • Natalia Egorova
  • Courtney Lang
  • Jin Cao
  • Jian Kong

Classical theories suggest placebo analgesia and nocebo hyperalgesia are based on expectation and conditioned experience. Whereas the neural mechanism of how expectation modulates placebo and nocebo effects during pain anticipation have been extensively studied, little is known about how experience may change brain networks to produce placebo and nocebo responses. We investigated the neural pathways of direct and observational conditioning for conscious and nonconscious conditioned placebo/nocebo effects using magnetoencephalography and a face visual cue conditioning model. We found that both direct and observational conditioning produced conscious conditioned placebo and nocebo effects and a nonconscious conditioned nocebo effect. Alpha band brain connectivity changes before and after conditioning could predict the magnitude of conditioned placebo and nocebo effects. Particularly, the connectivity between the rostral anterior cingulate cortex and middle temporal gyrus was an important indicator for the manipulation of placebo and nocebo effects. Our study suggests that conditioning can mediate our pain experience by encoding experience and modulating brain networks.

YNICL Journal 2019 Journal Article

Corrigendum to ‘Multivariate resting-state functional connectivity predicts responses to real and sham acupuncture treatment in chronic low back pain’ Neuroimage Clinical, 23, 2019, 101885

  • Yiheng Tu
  • Ana Ortiz
  • Randy L. Gollub
  • Jin Cao
  • Jessica Gerber
  • Courtney Lang
  • Joel Park
  • Georgia Wilson

The authors regret to find several errors that do not influence the main findings or conclusions.Specifically, we have found that the values of pre-and post-treatment clinical sub-scores for 'physical function' and 'sleep' in Fig. 4 contain errors.The corrected Fig. 4 is shown below: As a result, the Results section 3.3 (Page 6, right column): "Real and sham acupuncture significantly reduced PROMIS sub-scores in

YNIMG Journal 2019 Journal Article

Decreased structural connectivity and resting-state brain activity in the lateral occipital cortex is associated with social communication deficits in boys with autism spectrum disorder

  • Minyoung Jung
  • Yiheng Tu
  • Courtney Amanda Lang
  • Ana Ortiz
  • Joel Park
  • Kristen Jorgenson
  • Xue-Jun Kong
  • Jian Kong

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by atypical social communication and repetitive behaviors. In this study, we applied a multimodal approach to investigate brain structural connectivity, resting state activity, and surface area, as well as their associations with the core symptoms of ASD. Data from forty boys with ASD (mean age, 11. 5 years; age range, 5. 5–19. 5) and forty boys with typical development (TD) (mean age, 12. 3; age range, 5. 8–19. 7) were extracted from the Autism Brain Imaging Data Exchange II (ABIDE II) for data analysis. We found significantly decreased structural connectivity, resting state brain activity, and surface area at the occipital cortex in boys with ASD compared to boys with TD. In addition, we found that resting state brain activity and surface area in the lateral occipital cortex was negatively correlated with communication scores in boys with ASD. Our results suggest that decreased structural connectivity and resting-state brain activity in the occipital cortex may impair the integration of verbal and non-verbal communication cues in boys with ASD, thereby impacting their social development.

YNIMG Journal 2019 Journal Article

Identifying inter-individual differences in pain threshold using brain connectome: a test-retest reproducible study

  • Yiheng Tu
  • Binlong Zhang
  • Jin Cao
  • Georgia Wilson
  • Zhiguo Zhang
  • Jian Kong

Individuals are unique in terms of brain and behavior. Some are very sensitive to pain, while others have a high tolerance. However, how inter-individual intrinsic differences in the brain are related to pain is unknown. Here, we performed longitudinal test-retest analyses to investigate pain threshold variability among individuals using a resting-state fMRI brain connectome. Twenty-four healthy subjects who received four MRI sessions separated by at least 7 days were included in the data analysis. Subjects’ pain thresholds were measured using two modalities of experimental pain (heat and pressure) on two different locations (heat pain: leg and arm; pressure pain: leg and thumbnail). Behavioral results showed strong inter-individual variability and strong within-individual stability in pain threshold. Resting state fMRI data analyses showed that functional connectivity profiles can accurately identify subjects across four sessions, indicating that an individual’s connectivity profile may be intrinsic and unique. By using multivariate pattern analyses, we found that connectivity profiles could be used to predict an individual’s pain threshold at both within-session and between-session levels, with the most predictive contribution from medial-frontal and frontal-parietal networks. These results demonstrate the potential of using a resting-state fMRI brain connectome to build a ‘neural trait’ for characterizing an individual’s pain-related behavior, and such a ‘neural trait’ may eventually be used to personalize clinical assessments.

YNICL Journal 2019 Journal Article

Multivariate resting-state functional connectivity predicts responses to real and sham acupuncture treatment in chronic low back pain

  • Yiheng Tu
  • Ana Ortiz
  • Randy L. Gollub
  • Jin Cao
  • Jessica Gerber
  • Courtney Lang
  • Joel Park
  • Georgia Wilson

Despite the high prevalence and socioeconomic impact of chronic low back pain (cLBP), treatments for cLBP are often unsatisfactory, and effectiveness varies widely across patients. Recent neuroimaging studies have demonstrated abnormal resting-state functional connectivity (rsFC) of the default mode, salience, central executive, and sensorimotor networks in chronic pain patients, but their role as predictors of treatment responsiveness has not yet been explored. In this study, we used machine learning approaches to test if pre-treatment rsFC can predict responses to both real and sham acupuncture treatments in cLBP patients. Fifty cLBP patients participated in 4 weeks of either real (N = 24, age = 39.0 ± 12.6, 16 females) or sham acupuncture (N = 26, age = 40.0 ± 13.7, 15 females) treatment in a single-blinded trial, and a resting-state fMRI scan prior to treatment was used in data analysis. Both real and sham acupuncture can produce significant pain reduction, with those receiving real treatment experiencing greater pain relief than those receiving sham treatment. We found that pre-treatment rsFC could predict symptom changes with up to 34% and 29% variances for real and sham treatment, respectively, and the rsFC characteristics that were significantly predictive for real and sham treatment differed. These results suggest a potential way to predict treatment responses and may facilitate the development of treatment plans that optimize time, cost, and available resources.

YNIMG Journal 2019 Journal Article

Transient increased thalamic-sensory connectivity and decreased whole-brain dynamism in autism

  • Zening Fu
  • Yiheng Tu
  • Xin Di
  • Yuhui Du
  • Jing Sui
  • Bharat B. Biswal
  • Zhiguo Zhang
  • N. de Lacy

Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with social communication deficits and restricted/repetitive behaviors and is characterized by large-scale atypical subcortical-cortical connectivity, including impaired resting-state functional connectivity between thalamic and sensory regions. Previous studies have typically focused on the abnormal static connectivity in ASD and overlooked potential valuable dynamic patterns in brain connectivity. However, resting-state brain connectivity is indeed highly dynamic, and abnormalities in dynamic brain connectivity have been widely identified in psychiatric disorders. In this study, we investigated the dynamic functional network connectivity (dFNC) between 51 intrinsic connectivity networks in 170 individuals with ASD and 195 age-matched typically developing (TD) controls using independent component analysis and a sliding window approach. A hard clustering state analysis and a fuzzy meta-state analysis were conducted respectively, for the exploration of local and global aberrant dynamic connectivity patterns in ASD. We examined the group difference in dFNC between thalamic and sensory networks in each functional state and group differences in four high-dimensional dynamic measures. The results showed that compared with TD controls, individuals with ASD show an increase in transient connectivity between hypothalamus/subthalamus and some sensory networks (right postcentral gyrus, bi paracentral lobule, and lingual gyrus) in certain functional states, and diminished global meta-state dynamics of the whole-brain functional network. In addition, these atypical dynamic patterns are significantly associated with autistic symptoms indexed by the Autism Diagnostic Observation Schedule. These converging results support and extend previous observations regarding hyperconnectivity between thalamic and sensory regions and stable whole-brain functional configuration in ASD. Dynamic brain connectivity may serve as a potential biomarker of ASD and further investigation of these dynamic patterns might help to advance our understanding of behavioral differences in this complex neurodevelopmental disorder.

YNICL Journal 2019 Journal Article

Visual network alterations in brain functional connectivity in chronic low back pain: A resting state functional connectivity and machine learning study

  • Wei Shen
  • Yiheng Tu
  • Randy L. Gollub
  • Ana Ortiz
  • Vitaly Napadow
  • Siyi Yu
  • Georgia Wilson
  • Joel Park

Chronic low back pain (cLBP) is associated with widespread functional and structural changes in the brain. This study aims to investigate the resting state functional connectivity (rsFC) changes of visual networks in cLBP patients and the feasibility of distinguishing cLBP patients from healthy controls using machine learning methods. cLBP (n = 90) and control individuals (n = 74) were enrolled and underwent resting-state BOLD fMRI scans. Primary, dorsal, and ventral visual networks derived from independent component analysis were used as regions of interest to compare resting state functional connectivity changes between the cLBP patients and healthy controls. We then applied a support vector machine classifier to distinguish the cLBP patients and control individuals. These results were further verified in a new cohort of subjects. We found that the functional connectivity between the primary visual network and the somatosensory/motor areas were significantly enhanced in cLBP patients. The rsFC between the primary visual network and S1 was negatively associated with duration of cLBP. In addition, we found that the rsFC of the visual network could achieve a classification accuracy of 79.3% in distinguishing cLBP patients from HCs, and these results were further validated in an independent cohort of subjects (accuracy = 66.7%). Our results demonstrate significant changes in the rsFC of the visual networks in cLBP patients. We speculate these alterations may represent an adaptation/self-adjustment mechanism and cross-model interaction between the visual, somatosensory, motor, attention, and salient networks in response to cLBP. Elucidating the role of the visual networks in cLBP may shed light on the pathophysiology and development of the disorder.

YNIMG Journal 2018 Journal Article

Characterizing dynamic amplitude of low-frequency fluctuation and its relationship with dynamic functional connectivity: An application to schizophrenia

  • Zening Fu
  • Yiheng Tu
  • Xin Di
  • Yuhui Du
  • G.D. Pearlson
  • J.A. Turner
  • Bharat B. Biswal
  • Zhiguo Zhang

The human brain is a highly dynamic system with non-stationary neural activity and rapidly-changing neural interaction. Resting-state dynamic functional connectivity (dFC) has been widely studied during recent years, and the emerging aberrant dFC patterns have been identified as important features of many mental disorders such as schizophrenia (SZ). However, only focusing on the time-varying patterns in FC is not enough, since the local neural activity itself (in contrast to the inter-connectivity) is also found to be highly fluctuating from research using high-temporal-resolution imaging techniques. Exploring the time-varying patterns in brain activity and their relationships with time-varying brain connectivity is important for advancing our understanding of the co-evolutionary property of brain network and the underlying mechanism of brain dynamics. In this study, we introduced a framework for characterizing time-varying brain activity and exploring its associations with time-varying brain connectivity, and applied this framework to a resting-state fMRI dataset including 151 SZ patients and 163 age- and gender matched healthy controls (HCs). In this framework, 48 brain regions were first identified as intrinsic connectivity networks (ICNs) using group independent component analysis (GICA). A sliding window approach was then adopted for the estimation of dynamic amplitude of low-frequency fluctuation (dALFF) and dFC, which were used to measure time-varying brain activity and time-varying brain connectivity respectively. The dALFF was further clustered into six reoccurring states by the k-means clustering method and the group difference in occurrences of dALFF states was explored. Lastly, correlation coefficients between dALFF and dFC were calculated and the group difference in these dALFF-dFC correlations was explored. Our results suggested that 1) ALFF of brain regions was highly fluctuating during the resting-state and such dynamic patterns are altered in SZ, 2) dALFF and dFC were correlated in time and their correlations are altered in SZ. The overall results support and expand prior work on abnormalities of brain activity, static FC (sFC) and dFC in SZ, and provide new evidence on aberrant time-varying brain activity and its associations with brain connectivity in SZ, which might underscore the disrupted brain cognitive functions in this mental disorder.

v2026.09.13